PROJECT SUMMARY/ABSTRACT The purpose of the Genomics Core is to provide instrumentation, computational infrastructure, technical and analytic expertise, and guidance in order to broadly enable and to enhance the use of genomic analysis in Cystic Fibrosis (CF) research. Among other areas of research focus, the Genomics Core places a special emphasis in understanding host-microbe interactions in individuals with CF. The Aims of the Core are to: 1) Provide sequencing and computational resources to study microbial communities in the CF gut, 2) Provide cutting-edge sequencing and computational resources that advance research on pathogens associated with CF disease states, 3) Provide advanced services to understand gene expression and molecular physiology of human cells that are relevant to CF disease states, and 4) Develop novel technologies for the genome-scale analysis of CF microbiology. These aims will be fulfilled by providing UW CF researchers with consultative, production, and analytical services relevant to the following domains: i. Consultation on genomic methods and experimental design. ii. Data Analysis, Data Management, and Data Sharing Services. iii. Bacterial whole genome sequencing. iv. Metagenomic and 16S rRNA Microbiome data generation and Analysis. v. Transcriptome sequencing (RNA-Seq) and targeted gene expression analysis (qRT-PCR). vi. Gut microbe quantitation by Digital Droplet PCR (dPCR). vii. New sequencing technology innovation. In addition to defining the microbiome of the gut at various timepoints and in various disease states of individuals with CF, the Core will play a primary role in driving projects to define how the microbiomes of the gastrointestinal (GI) and respiratory tracts change across the full lifespan of patients with CF, and to understand how the administration of highly effective CFTR modulators changes the composition and metabolic functions of the microbiome and its interface with host cells.